How Common is Transthyretin Amyloid Cardiomyopathy (ATTR-cm)? Prevalence, Causes, and More

Transthyretin amyloid cardiomyopathy may be classified into two types: wild-type transthyretin amyloid cardiomyopathy (wATTR-cm) or hereditary transthyretin amyloid cardiomyopathy (hATTR-cm). Despite being particularly challenging, but early diagnosis and treatment are the best plan of action for either type.

What is the Prevalence of Transthyretin Amyloid Cardiomyopathy?

Unfortunately, all the data concerning transthyretin amyloid cardiomyopathy prevalence is very limited. Dr. Aeshita Dwivedi, a cardiologist at Lenox Hill Hospital in New York, explains, "ATTR cardiomyopathy is, unfortunately, an underdiagnosed condition." The prevalence of ATTR-cm is increasing lately due to improved awareness and diagnostic capabilities.

Researchers believe that there are probably many more cases that we aren't yet aware of due to misdiagnosis or underdiagnosis.

This condition frequently goes underdiagnosed in many people due to the following reasons:

• This condition shares a lot of features with other diseases
• There was a lack of sensitive diagnostic techniques to identify the disease
• The symptoms of ATTR-cm can mimic those of other conditions
• Low awareness of the disease (Luckily, it received increased attention in diagnosis and treatment recently)
• It differs from region to region
• The prevalence is different in those who have wild-type ATTR-cm and hereditary ATTR-cm

As a result, it's a challenge to pinpoint an exact percentage of the number of cases with transthyretin amyloid cardiomyopathy but according to data published on The Portal of Rare Diseases and Orphan Drugs, the prevalence of wild-type amyloidosis (wATTR-cm) is estimated, on average, at 1/5,800 worldwide.

What is Transthyretin Amyloid Cardiomyopathy?

To break it down, below is a list of the medical terminologies and what they refer to:

• Transthyretin: The protein responsible for transporting vitamin A and thyroxin (a type of thyroid hormone) to the liver and other body parts. When it's mutated, it folds on itself and causes amyloid deposits.

• Amyloidosis: Refers to the condition of built-up misfolded transthyretin proteins (fibrils) that makes the walls of the heart thicker, stiffer, and unable to function properly.

• Cardiomyopathy: A term meaning the disease of the muscles of the heart (myocardium) that makes it unable to pump blood to the body. The heart keeps on struggling to do its normal functions finally leading to heart failure.

These build-ups lead to the disruption of the normal heart functions in pumping blood through the body leading to several complications including the following:

• Heart block
• Arrhythmias (irregular pattern of heartbeats)
• Atrial fibrillation (a highly irregular pulse rate)
• Congestive heart failure (the heart muscle doesn't pump blood correctly as it should)

What Causes Transthyretin Amyloid Cardiomyopathy?

Regardless of the type of transthyretin amyloid cardiomyopathy (wild or hereditary), the cause is the same which is a mutation in the TTR gene responsible for producing transthyretin amyloid protein.

When this gene is mutated, the body starts to produce an abnormal protein that folds incorrectly and forms clumps of transthyretin amyloid proteins in the form of fibrils that accumulate on the heart and other different body parts leading to organ damage over time.

• Hereditary Transthyretin Amyloid Cardiomyopathy (hATTR-cm)

From its name, this type runs in families and is carried from generation to generation with a faulty transthyretin gene resulting in clumps of proteins. These clumps deposit on several organs like the heart, kidney, or nerves. Symptoms usually manifest in individuals between the ages of 20-80 years old.

The best way to conclusively diagnose hereditary transthyretin amyloid cardiomyopathy is by doing a genetic test.

• Wild-type Transthyretin Amyloid Cardiomyopathy (wATTR-cm)

Unlike hereditary transthyretin amyloid cardiomyopathy, this type doesn't run in families but rather occurs sporadically and affects the heart. Additionally, it may cause other conditions like carpal tunnel syndrome (a condition that causes numbness, tingling, and pain in the hands).

Symptoms for this type generally manifest in older individuals (older than 65 years old), primarily males.

What are the symptoms of Transthyretin Amyloid Cardiomyopathy?

Symptoms of transthyretin amyloid cardiomyopathy may differ from patient to patient according to the following parameters:

• Type of transthyretin amyloid cardiomyopathy (hereditary or wild type)
• The overall health of the patient
• Other underlying conditions
• Patient's age

So, while some may have debilitating symptoms that disrupt their everyday life, others may experience no symptoms and remain undiagnosed. These symptoms include the following:

• Shortness of breath
• Stomach bloating
• Fatigue
• Irregular heartbeat
• Dizziness
• Coughing
• Wheezing
• Confusion
• Chest pains
• Enlarged liver
• Swelling in the leg

Dr. Philip Weintraub, a cardiologist at NYU Langone Health adds, "A lot of [the symptoms] based upon the fact that without the necessary oxygen that needs to be in your bloodstream, it'll compromise the body's ability to function properly."

These symptoms are frequently mistaken with other health conditions, but once transthyretin amyloid cardiomyopathy (ATTR-cm) is suspected, your doctor can proceed with performing diagnostic tests to confirm the diagnosis, these tests include the following:

• Imaging studies (ex. MRI) on the heart
• Genetic testing (if it's hereditary transthyretin amyloid cardiomyopathy)
• Taking a biopsy from the affected organ (biopsy from the heart muscle)
• Electrocardiogram or ECG (a test to check your heart's electrical activity and rhythm)
• Echocardiogram or echo (a type of ultrasound scan to check the heart and neighboring blood vessels)

A recent study published in 2021 in the Journal of Cardiology and Therapy, reviewed the scientific literature on the impact of delayed diagnosis of transthyretin amyloid cardiomyopathy on patients and concluded that many patients experienced misdiagnosis through the years even though there were some inconsistencies with their declared diagnosis.

Accordingly, the authors recommended more efforts be put to use to expedite the diagnostic process to ultimately benefit patients with early treatment. They add "The recognition of early red flags, the introduction of noninvasive diagnostic techniques, and the availability of disease-modifying therapies are expected to increase disease awareness and facilitate early diagnosis."

Once the diagnosis has been confirmed, your doctor will discuss your available treatment options, these may include the following:

• Medications to ease your symptoms
• Medications to reduce amyloidosis (misfolded proteins accumulation)
• Organ transplantation (in advanced stages)

A study published in 2021 in the European Journal of Heart Failure, revealed that experts in the field agreed to follow a checklist with a set of parameters to monitor patients with transthyretin amyloid cardiomyopathy and assess their disease progression in a relatively short period (6-12 months of diagnosis) to help with treatment.

This means that with further investigations and data collection, managing this condition in the upcoming years to come will be much easier.

The Bottom Line

Even though transthyretin amyloid cardiomyopathy is rare, it's extremely challenging to diagnose. Early diagnosis plays an important role in better treatment outcomes for patients.

It's recommended to get tested if you have a family history of heart failure or transthyretin amyloid cardiomyopathy. Moreover, if you've ever experienced any of the previously mentioned symptoms, consult your doctor immediately.

Questions to Ask Your Doctor

• Do I have wild-type transthyretin amyloid cardiomyopathy or hereditary transthyretin cardiomyopathy?
• What are my treatment options?
• Will I need organ transplantation?
• Are there any side effects of the medications?
• How can I prevent any complications from occurring?
• How can I improve my quality of life with this disease?
• Are there any support groups you recommend for me?
• What are my chances of complete recovery If I enroll in a clinical trial?

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